Monday, Nov. 14, 2005Bitter PillsThey're prescribed to millions, but do the new antidepressants work? And are they worth the risk? BY DANIEL WILLIAMS

There's really nothing funny about what happened to Rebekah Beddoe,
except maybe for a little black comedy at the end. In 1999, a
psychiatrist diagnosed her with postnatal depression, which she
probably didn't have, and for the next three years multiple doctors
treated her with drugs that she almost certainly didn't need. As
episodes of deliberately cutting herself progressed to bouts of mental
torment and suicide attempts, Beddoe's carers, concluding that her
illness was worsening, kept upping her dosages and trying new
medications. Nothing worked. Eventually, Beddoe acted on a different
idea. Without telling anyone, she weaned herself off the drugs and
gradually became well again. Her psychiatrist at the time assumed he
was responsible for Beddoe's recovery. She remembers watching him one
day from the other side of his desk, thinking that this eminent doctor
was congratulating himself on having the skill to concoct precisely the
right drug regimen. "I could also see his relief," Beddoe says. "It had
been a difficult case, but he'd finally cracked it."

These days Beddoe, 33, spends much of her time at home in Melbourne
reading up on
psychiatry while working on a book about her ordeal. She's certain that
what made her sick were side effects of the most commonly prescribed
class of antidepressants, the selective serotonin reuptake inhibitors
(SSRIs). A pharmaceutical phenomenon that began with fluoxetine
(Prozac) in the late 1980s, the SSRIs rode a wave of gushing publicity
to usurp the older antidepressants, the tricyclics, and reap a fortune
for their makers: worldwide sales now exceed $20 billion a year. But
the honeymoon is over. Even doctors who swear by SSRIs and newer
variants concede that 1-2% of patients have a severe negative reaction
to these drugs. That's a small percentage. But it's a small percentage
of a very large number. Intractable misery is rife, it seems: in
Australia last year, 12 million prescriptions for antidepressants were
dispensed through the federal government's Pharmaceutical Benefits
Scheme (up from 8.2 million in 1998), a figure equating to more than a
million users. Do the math, says Sydney forensic psychiatrist Yolande
Lucire: if only 1% of users suffer terrible side effects that aren't
recognized for what they are, that's more than 10,000 Australians
who've recently been disabled by a drug that was supposed to help them.
"That would be enough to fill the beds in every mental hospital in the
country."

Lucire's is one voice in a small but growing international chorus of
SSRI skeptics. As well as highlighting side effects, these critics
question whether the SSRIs do what they're supposed to do in a
significant proportion of cases. Based on fresh analyses of
clinical-trial results, some researchers have concluded that the drugs
are scarcely more effective than a placebo in alleviating depression.
"I think they are more or less completely useless," says Dr. Joanna
Moncrieff, senior lecturer in social and community psychiatry at
University College London. In an article published earlier this year in
the British Medical Journal, Moncrieff and coauthor Irving Kirsch,
professor of psychology at the University of Plymouth, argued that it
was time for "a thorough reevaluation of current approaches to
depression and further development of alternatives to drug treatment."
Seldom had a piece about antidepressants so explicitly challenged the
reigning orthodoxy in the mainstream medical press, and it was hailed
as a breakthrough by those who oppose what they see as disease
mongering by the drug industry and other groups.
The drug skeptics have had other recent victories. In the U.S. last
year, the Food and Drug Administration told the drug companies to
harden their warnings about the potential side effects of SSRIs. The
companies' prescriber information must now feature a black-box warning
- the strongest available - stating that in trials "antidepressants
increased the risk of suicidal thinking and behavior" in children and
adolescents with depression and other psychiatric disorders. The fda is
reviewing the results of several trials to determine whether a similar
warning should be introduced for adults. British health authorities
have gone further: in September, the National Health Service told
doctors to stop prescribing antidepressants to under-18s in the early
stages of treatment because of the link with suicidal thinking.
Compared with its American and British counterparts, Australia's
Therapeutic Goods Administration has taken a gentler line. Last year it
reminded doctors that no antidepressant is approved in Australia for
the treatment of depression in under-18s - though it knows many
thousands of Australian teenagers with that diagnosis are on the drugs.
In August, a TGA bulletin acknowledged a probable link between the
SSRIs and suicidal tendencies in children and adults, but overall
endorsed the drugs. Still, for perhaps the first time since the SSRIs
came on the scene, those who believe the medical profession has lost
its way in treating depression feel they have some momentum. "The
(non-drug) approach is growing," says Dr. Jon Jureidini, head of the
department of psychological medicine at the Women's and Children's
Hospital in Adelaide. "I'm probably at one end of the spectrum, but
there would now be plenty of psychiatrists who would be very
conservative prescribers."